Antifungal susceptibility pattern of Candida auris strains: Analysis of clinical strains in a tertiary-care educational university hospital.

Herein, we aimed to investigate the antifungal susceptibility pattern of Candida auris clinical strains in our setting Bahrain Oncology Center-King Hamad University Hospital-Bahrain. C. auris strains isolated from different clinical specimens in the Microbiology Laboratory from October-2021 to November-2022 were evaluated. Species-level identification of fungi was performed by MALDI-TOF (Bruker, Germany). Minimum inhibitory concentration (MIC) was determined either by E-test strips or by MICRONAUT MIC system based on CDC guidelines for C. auris antifungal interpretation. Fluconazole, amphotericin-B, voriconazole, and caspofungin susceptibility data of the clinical strains were analyzed. A total of 40 clinical isolates were included: 25% were blood culture isolates, 65% were urinary, and 10% were soft tissue isolates. Only 29 strains could be tested for amphotericin-B and 32 for voriconazole. Overall resistance pattern was as follows: 100% resistance to fluconazole, 2.5% resistance to caspofungin, and 0% resistance to amphotericin b. Median voriconazole MIC was 0.015 ug/ml (min 0.08, max= 0.064 ug/ml). We had no fluconazole-sensitive strain and only one caspofungin-resistant strain. A single isolate (2.5%), which was associated with candidemia, demonstrated resistance to two antifungal agents: fluconazole and caspofungin. No triple or quadruple drug resistant strain existed.

Can daily bathing with 4% chlorhexidine + daily chlorhexidine wipe for 1 week be effective in decolonizing Candida auris colonization?

BACKGROUND: Herein, it is aimed to present the decolonizing rates of Candida auris colonized cases after daily bathing with 4% chlorhexidine plus daily cleaning with 4% chlorhexidine wipe for 1 week (will be mentioned as DCHX). METHODS: The study period was from October, 2021, to November, 2022. Inclusion criteria were (i) age > 18, (ii) receiving DCHX, (iii) proven C. auris carrier on auricular, or axillar or inguinal swab surveillance cultures up to 5-day period before DCHX. Cases with three consecutive negative surveillance cultures 3 days apart were considered to be decolonized. RESULTS: A total of 38 cases [14 female, aged 61.8 ± 15.5 years] fulfilled the inclusion criteria. Six (15.8%), 23 (60.1%), and 22 cases (57.8%) were postauricular, inguinal, and axillary culture positive, respectively. Only three cases (7.9%) were triple culture positive. Nine cases (23.7%) had three consequent negative surveillance cultures after DCHX and were considered to be decolonized. There was no significant difference in decolonization rates of concomitant only antibiotic receiving cohort vs. concomitant antifungal + antibiotic receiving cohort (5/16 vs. 2/8, p = 1) were decolonized similarly. Of the nine C. auris decolonized cases, two developed C. auris infection in 30 days follow-up after decolonization. However, 10 (34.5%) of 29 non-decolonized cases developed C. auris infection (p: 0.450) within 30 days after surveillance culture positivity. Over all cohorts, day 30 mortality was 23.7% (9/38). CONCLUSION: In conclusion, based on our observational and relatively small uncontrolled series, it appears that DCHX is not very effective in decolonizing C. auris carriers (especially in cases who are C. auris colonized in > 1 areas), although it is not completely ineffective.

Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel.

Germline variants in BRCA1 and BRCA2 (BRCA1/2) genes are the most common cause of hereditary breast cancer. However, a significant number of cases are not linked to these two genes and additional high-, moderate- and low-penetrance genes have been identified in breast cancer. The advent of next-generation sequencing (NGS) allowed simultaneous sequencing of multiple cancer-susceptibility genes and prompted research in this field. So far, cancer-predisposition genes other than BRCA1/2 have not been studied in the population of Bahrain. We performed a targeted NGS using a multi-panel covering 180 genes associated with cancer predisposition to investigate the spectrum and frequency of germline variants in 54 women with a positive personal and/or family history of breast cancer. Sequencing analysis revealed germline variants in 29 (53.7%) patients. Five pathogenic/likely pathogenic variants in four DNA repair pathway-related genes were identified in five unrelated patients (9.3%). Two BRCA1 variants, namely the missense variant c.287A>G (p.Asp96Gly) and the truncating variant c.1066C>T (p.Gln356Ter), were detected in two patients (3.7%). Three variants in non-BRCA1/2 genes were detected in three patients (1.85% each) with a strong family history of breast cancer. These included a monoallelic missense variant c.1187G>A (p.Gly396Asp) in MUTYH gene, and two truncating variants namely c.3343C>T (p.Arg1115Ter) in MLH3 gene and c.1826G>A (p.Trp609Ter) in PMS1 gene. Other variants of uncertain significance (VUS) were also detected, and some of them were found together with the deleterious variants. In this first application of NGS-based multigene testing in Bahraini women with breast cancer, we show that multigene testing can yield additional genomic information on low-penetrance genes, although the clinical significance of these genes has not been fully appreciated yet. Our findings also provide valuable epidemiological information for future studies and highlight the importance of genetic testing, and an NGS-based multigene analysis may be applied supplementary to traditional genetic counseling.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Predictors of Coronary Artery Disease Progression among High-risk Patients with Recurrent Symptoms.

BACKGROUND: Despite the availability of new potent medical therapies, the rate of progression of angiographic coronary artery disease (CAD) is not well described. The aim of this analysis is to describe the rate and predictors of progression of CAD among patients with recurrent symptoms. MATERIALS AND METHODS: We reviewed 259 patients (mean age 61 ± 11 years, 70% males) who underwent two coronary angiograms between 2008 and 2013. Progressive CAD was defined as obstructive CAD in a previously disease-free segment or new obstruction in a previously nonobstructive segment. Patients who had coronary artery bypass surgery between these two angiograms were excluded from the analysis. Multivariate logistic regression was used to determine the independent predictors of progression of CAD. RESULTS: The included cohort had a high prevalence of coronary risk factors; hypertension (71%), diabetes (69%), and dyslipidemia (75%). Despite adequate medical therapy, more than half of the patients (61%) had CAD progression. Using multivariate logistic regression, a drop in the left ventricular ejection fraction (LVEF) by more than 5% was the predictor of CAD progression (adjusted odds ratio 5.8, P = 0.042, 95% confidence interval 1.1-31.2). CONCLUSION: Among high-risk patients with recurrent symptoms, the short-term rate of progression of CAD is high. A drop in LVEF >5% is a predictor of CAD progression. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis.

BACKGROUND: The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention. METHODS: Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox's proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance. RESULTS: On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (≤35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months). CONCLUSIONS: Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.

Successful pregnancies after combined human leukocyte antigen direct genotyping and preimplantation genetic diagnosis utilizing multiple displacement amplification.

OBJECTIVE: To devise a new and simple technique to help select normal embryos that are human leukocyte antigen (HLA) matched to their affected siblings for diseases, such as beta-thalassemia or sickle cell anemia, which are common in this part of the world. METHODS: This study was conducted between March 2008 and April 2011 at the preimplantation Genetic Diagnosis Laboratory, Saad Specialist Hospital, Al-Khobar, Kingdom of Saudi Arabia. Embryos were obtained after 7 in vitro fertilization preimplantation genetic diagnosis (IVF-PGD) cycles. Single cells were biopsied, and extracted DNA was amplified by the multiple displacement amplification (MDA) technique. Amplified DNA was then tested for mutations in the beta-globin gene, and directly HLA typed using a sequence specific primer technique. RESULTS: We report 7 families that underwent 7 PGD cycles with HLA typing and direct HLA loci-typing using an HLA conventional commercial kit. Two patients had PGD and HLA typing for class I and II, while the other 5 had class II. The PGD cycles resulted in 3 pregnancies out of 5 patients who had HLA matched and normal embryos. One family had a successful hematopoietic stem cell transplant. CONCLUSION: This report demonstrates the first clinical application of PGD coupled with direct HLA loci-typing of DNA amplified by MDA from a single cell.

Age of 40 years or younger is an independent risk factor for locoregional failure in early breast cancer: a single-institutional analysis in saudi arabia.

Background. This study was undertaken to evaluate the impact of prognostic factors on the locoregional failure-free survival of early breast cancer patients. Methods. In this single-institutional study, 213 breast cancer patients were retrospectively analysed. Fifty-five of 213 patients were ≤40 years of age at diagnosis. The impact of patient- or treatment-related factors on the locoregional failure-free survival was assessed using the Kaplan-Meier method. The simultaneous impact of factors on the locoregional failure-free survival was assessed using the Cox proportional hazards regression analysis. Results. The median follow-up time of the censored patients was 22 months (mean 28 months, range 3-92 months). On univariate analysis, statistically significant factors for the locoregional failure-free survival were the age (≤40 versus >40 years), T stage (Tis, T0-2 versus T3-4), molecular tumor type (luminal A versus luminal B, Her2neu overexpression, or triple negative), and lymphovascular status (LV0 versus LV1). On multivariate analysis, age and T stage remained statistically significant. Conclusions. Being 40 years or younger has a statistically significant independent adverse impact on the locoregional failure-free survival of patients with early breast cancer.

Molecular spectrum of alpha-thalassemia mutations in microcytic hypochromic anemia patients from Saudi Arabia.

AIM: To describe the molecular spectrum of alpha-thalassemia molecular defects in a population sample of Saudi Arabian patients from the eastern province. METHODS: DNA was extracted from 41 patients suffering from microcytic, hypochromic anemia. We screened the alpha-globin gene for deletional and nondeletional mutations. RESULTS: Besides the common Rightward alpha(-3.7) (64%), polyA mutation (AATAAA to AATAAG) was found (41%). The risk of developing hemoglobin H (HBH) disease in case of homozygous polyA inheritance highlights the importance of detecting such mutation. CONCLUSION: The high prevalence of polyA mutation and the lack of any clue in discerning such alpha-thalassemia defect by routine complete blood count (CBC) necessitate a strict molecular screening of all cases presenting with hypochromic microcytic anemia.